Exp Clin Endocrinol Diabetes 2013; 121 - P103
DOI: 10.1055/s-0033-1336776

Experimental immunomodulation with 25(OH)D3 to preserve ß-cell integrity and function in early Type 1 Diabetes

E Ramos-Lopez 1, S Mauf 1, WA Mann 2, T Bottler 3, M Penna-Martinez 1, K Badenhoop 1, M von Herrath 3
  • 1Department of Internal Medicine I, Division of Endocrinology, Diabetes and Metabolism, University Hospital Frankfurt am Main, Frankfurt am Main, Germany
  • 2Endokrinologikum Frankfurt, Academic Teaching Unit of the University Hospital Frankfurt am Main, Frankfurt am Main, Germany
  • 3Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California, United States

Introduction: At the diagnosis of type 1 diabetes (T1D) no therapy can stop the further destruction of remaining β-cells. Although the beneficial effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has been proven, its use is limited. However, the effects of 25-hydroxyvitamin D3 (25(OH)D3), the precursor of 1,25(OH)2D3, in vivo are unknown. We tested a) the immuneffectes of 25(OH)D3 in human monocytes in vitro and b) in an animal model (RIP-LCMV-GP-mouse-system of T1D) in vivo if 25(OH)D3 was able to protect the remaining ß-cells from the further destruction by modulating the course of the disease.

Methods: a) In vitro, monocytes (mØ) from T1D-patients (n = 12) were cultured with and without 25(OH)D3. The differentiation of mØ into dendritic cells (DCs) was tested by FACS. b) In vivo, immediately after the diagnosis of T1D, the RIP-LCMV-mice were treated with 25(OH)D3 (n = 27) or placebo (n = 14). Spleens were removed to investigate the influence of 25(OH)D3 on regulatory T-cells (Tregs), myeloid (mDCs) and plasmacytoid (pDCs) DCs by FACS.

Results: a) In vitro 25(OH)D3 inhibited the differentiation of mØ into DCs (CD11c+/CD14-/CD83+/CD123-/low+; 9.1% vs. 42.2%, p < 0.001) but there was an increase of intermediary cells (CD11c+/CD14+/CD83+/CD123-/low+; 77.8% vs. 49.1%; p < 0.001). b) In vivo 74% of the mice treated with 25(OH)D3 responded to the treatment in contrast to 28% in the placebo group (p < 0.001). However no differences in the distribution of mDC, pDC or Tregs were observed.

Conclusion: 25(OH)D3 modulated in vitro the immune system at least by inhibiting the differentiation of monocytes into dendritic cells of T1D patients. At diabetes manifestation 25(OH)D3 can modulate the course of T1D in RIP-LCMV-GP mice. Since we did not observe changes in the distribution of the mDCs, pDcs or Tregs in the spleens, this may point to a local and specific effect of 25(OH)D3 in the pancreas or its draining lymph nodes.